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Forschungsdatenbank PMU-SQQUID

Interferon-beta stabilizes barrier characteristics of the blood-brain barrier in four different species in vitro.
Kraus, J; Voigt, K; Schuller, AM; Scholz, M; Kim, KS; Schilling, M; Schäbitz, WR; Oschmann, P; Engelhardt, B;
MULT SCLER. 2008; 14(6): 843-852.
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Kraus Jörg

Abstract

Background Blood-brain barrier (BBB) breakdown is an early event in the pathogenesis of multiple sclerosis (MS). In a previous study we have found a direct stabilization of barrier characteristics after treatment of bovine brain capillary endothelial cells (BCECs) with human recombinant interferon-beta-1a (IFN-beta-1 alpha) in an in vitro BBB model. In the present study we examined the effect of human recombinant IFN-beta-1 alpha on the barrier properties of BCECs derived from four different species including humans to predict treatment efficacy of IFN-beta-1 alpha in MS patients. Methods We used primary bovine and porcine BCECs, as well as human and murine BCEC cell lines. We investigated the influence of human recombinant IFN-beta-1 alpha on the paracellular permeability for 3H-inulin and 14C-sucrose across monolayers of bovine, human, and murine BCECs. In addition, the transendothelial electrical resistance (TEER) was determined in in vitro systems applying porcine and murine BCECS. Results We found a stabilizing effect on the barrier characteristics of BCECs after pretreatment with IFN-beta-1 alpha in all applied in vitro models: addition of IFN-beta-1 alpha resulted in a significant decrease of the paracellular permeability across monolayers of human, bovine, and murine BCECs. Furthermore, the TEER was significantly increased after pretreatment of porcine and murine BCECs with IFN-beta-1 alpha. Conclusion Our data suggest that BBB stabilization by IFN-beta-1 alpha may contribute to its beneficial effects in the treatment of MS. A human in vitro BBB model might be useful as bioassay for testing the treatment efficacy of drugs in MS.


Useful keywords (using NLM MeSH Indexing)

Adjuvants, Immunologic/pharmacology*

Animals

Astrocytes/cytology

Blood-Brain Barrier/drug effects*

Blood-Brain Barrier/immunology

Capillary Permeability/drug effects

Capillary Permeability/immunology

Cattle

Cells, Cultured

Coculture Techniques

Dose-Response Relationship, Drug

Drug Interactions

Endothelial Cells/cytology

Endothelial Cells/drug effects*

Histamine/pharmacology

Histamine Agonists/pharmacology

Interferon-beta/pharmacology*

Mice

Rats

Species Specificity

Swine


Find related publications in this database (Keywords)

blood-brain barrier
cell culture
endothelial cells
immunology
interferon-beta
multiple sclerosis